钆塞酸二钠增强磁共振成像在肝细胞癌生物学行为评估中的应用进展

doi:10.3969/j.issn.1674-8115.2022.01.020

摘要/Abstract

摘要：

肝细胞癌是肝脏最常见的原发性恶性肿瘤，是癌症相关死亡的第三大原因。钆塞酸二钠（gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid，Gd-EOB-DTPA）为目前常用的新型肝脏特异性对比剂，其诊断小肝细胞癌的敏感度和特异度均可高于90%。肝细胞癌的早期诊断可使患者临床获益，但肝细胞癌作为高度异质性肿瘤，其生物学行为也是影响预后的关键因素。Gd-EOB-DTPA增强磁共振成像（Gd-EOB-DTPA-enhanced magnetic resonance imaging，EOB-MRI）在识别肝细胞癌分子分型、评估免疫微环境、预测微血管侵犯以及术后复发等方面均能提供相关信息。该文即对EOB-MRI在肝细胞癌生物学行为评估中的应用进展作一综述，以期为肝细胞癌的诊断和治疗提供参考。

关键词: 肝细胞癌, 钆塞酸二钠, 磁共振成像, 分子分型, β-连环蛋白, 免疫微环境, 微血管侵犯, 复发

Abstract:

Hepatocellular carcinoma is the most common primary malignant tumor of liver tumors and ranked as the third leading cause of cancer death. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is a new hepatocyte-specific contrast agent commonly used at present. Its sensitivity and specificity for the diagnosis of small hepatocellular carcinoma can both be over 90%. Early diagnosis of hepatocellular carcinoma can benefit patients clinically, but as hepatocellular carcinoma is a highly heterogeneous tumor, the tumor biological behavior is also a key factor affecting the prognosis. Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) can provide relevant information about identification of molecular typing, evaluation of immune microenvironment, and prediction of microvascular invasion and postoperative recurrence in hepatocellular carcinoma. This article reviews the research progress of EOB-MRI in the evaluation of biological behavior of hepatocellular carcinoma to provide reference for the diagnosis and treatment of hepatocellular carcinoma.

Key words: hepatocellular carcinoma (HCC), gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), magnetic resonance imaging (MRI), molecular classification, β-catenin, immune microenvironment, microvascular invasion (MVI), recurrence

中图分类号:

R445.2

王亦欢, 李若坤, 种欢欢, 严福华. 钆塞酸二钠增强磁共振成像在肝细胞癌生物学行为评估中的应用进展[J]. 上海交通大学学报(医学版), 2022, 42(1): 130-134.

Yihuan WANG, Ruokun LI, Huanhuan CHONG, Fuhua YAN. Research progress of Gd-EOB-DTPA-enhanced magnetic resonance imaging in the evaluation of biological behavior of hepatocellular carcinoma[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(1): 130-134.

参考文献 44

1	FORNER A, REIG M, BRUIX J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314.
2	LI J, WANG J, LEI L, et al. The diagnostic performance of gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced multi-detector computed tomography in detecting hepatocellular carcinoma: a meta-analysis of eight prospective studies[J]. Eur Radiol, 2019, 29(12): 6519-6528.
3	KIERANS A S, KANG S K, ROSENKRANTZ A B. The diagnostic performance of dynamic contrast-enhanced MR imaging for detection of small hepatocellular carcinoma measuring up to 2 cm: a meta-analysis[J]. Radiology, 2016, 278(1): 82-94.
4	REBOUISSOU S, NAULT J C. Advances in molecular classification and precision oncology in hepatocellular carcinoma[J]. J Hepatol, 2020, 72(2): 215-229.
5	UENO A, MASUGI Y, YAMAZAKI K, et al. OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma[J]. J Hepatol, 2014, 61(5): 1080-1087.
6	KITAO A, ZEN Y, MATSUI O, et al. Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging: correlation with molecular transporters and histopathologic features[J]. Radiology, 2010, 256(3): 817-826.
7	KITAO A, MATSUI O, YONEDA N, et al. Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background[J]. Eur Radiol, 2020, 30(6): 3438-3447.
8	CHEN J, WU Z, XIA C, et al. Noninvasive prediction of HCC with progenitor phenotype based on gadoxetic acid-enhanced MRI[J]. Eur Radiol, 2020, 30(2): 1232-1242.
9	CHOI S Y, KIM S H, PARK C K, et al. Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study[J]. Radiology, 2018, 286(3): 897-908.
10	WANG W, GU D, WEI J, et al. A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid-enhanced MRI[J]. Eur Radiol, 2020, 30(5): 3004-3014.
11	OURA K, MORISHITA A, TANI J, et al. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: a review[J]. Int J Mol Sci, 2021, 22(11): 5801.
12	CHEN S, FENG S, WEI J, et al. Pretreatment prediction of immunoscore in hepatocellular cancer: a radiomics-based clinical model based on Gd-EOB-DTPA-enhanced MRI imaging[J]. Eur Radiol, 2019, 29(8): 4177-4187.
13	GALON J, MLECNIK B, BINDEA G, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours[J]. J Pathol, 2014, 232(2): 199-209.
14	GABRIELSON A, WU Y, WANG H, et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC[J]. Cancer Immunol Res, 2016, 4(5): 419-430.
15	RUIZ DE GALARRETA M, BRESNAHAN E, MOLINA-SÁNCHEZ P, et al. β-catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma[J]. Cancer Discov, 2019, 9(8): 1124-1141.
16	KUDO M. Gd-EOB-DTPA-MRI could predict WNT/β-catenin mutation and resistance to immune checkpoint inhibitor therapy in hepatocellular carcinoma[J]. Liver Cancer, 2020, 9(5): 479-490.
17	SPRANGER S, BAO R Y, GAJEWSKI T F. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity[J]. Nature, 2015, 523(7559): 231-235.
18	HARDING J J, NANDAKUMAR S, ARMENIA J, et al. Prospective genotyping of hepatocellular carcinoma: clinical implications of next-generation sequencing for matching patients to targeted and immune therapies[J]. Clin Cancer Res, 2019, 25(7): 2116-2126.
19	KUBO A, SUDA G, KIMURA M, et al. Characteristics and lenvatinib treatment response of unresectable hepatocellular carcinoma with iso-high intensity in the hepatobiliary phase of EOB-MRI[J]. Cancers, 2021, 13(14): 3633.
20	SUN L, MU L W, ZHOU J, et al. Imaging features of gadoxetic acid-enhanced MR imaging for evaluation of tumor-infiltrating CD8 cells and PD-L1 expression in hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2021: 1-14.
21	HECTORS S J, LEWIS S, BESA C, et al. MRI radiomics features predict immuno-oncological characteristics of hepatocellular carcinoma[J]. Eur Radiol, 2020, 30(7): 3759-3769.
22	RENZULLI M, BROCCHI S, CUCCHETTI A, et al. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? [J]. Radiology, 2016, 279(2): 432-442.
23	MIN J H, LEE M W, PARK H S, et al. Interobserver variability and diagnostic performance of gadoxetic acid-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma[J]. Radiology, 2020, 297(3): 573-581.
24	LEE S, KIM S H, LEE J E, et al. Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma[J]. J Hepatol, 2017, 67(3): 526-534.
25	RHEE H, AN C, KIM H Y, et al. Hepatocellular carcinoma with irregular rim-like arterial phase hyperenhancement: more aggressive pathologic features[J]. Liver Cancer, 2019, 8(1): 24-40.
26	FAN Y F, YU Y X, WANG X M, et al. Texture analysis based on Gd-EOB-DTPA-enhanced MRI for identifying vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma[J]. J Hepatocell Carcinoma, 2021, 8: 349-359.
27	HONG S B, CHOI S H, KIM S Y, et al. MRI features for predicting microvascular invasion of hepatocellular carcinoma: a systematic review and meta-analysis[J]. Liver Cancer, 2021, 10(2): 94-106.
28	YANG L, GU D, WEI J, et al. A radiomics nomogram for preoperative prediction of microvascular invasion in hepatocellular carcinoma[J]. Liver Cancer, 2019, 8(5): 373-386.
29	FENG S T, JIA Y, LIAO B, et al. Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI[J]. Eur Radiol, 2019, 29(9): 4648-4659.
30	CHONG H H, YANG L, SHENG R F, et al. Multi-scale and multi-parametric radiomics of gadoxetate disodium-enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma ≤ 5 cm[J]. Eur Radiol, 2021, 31(7): 4824-4838.
31	WEI J W, JIANG H Y, ZENG M S, et al. Prediction of microvascular invasion in hepatocellular carcinoma via deep learning: a multi-center and prospective validation study[J]. Cancers, 2021, 13(10): 2368.
32	CHOI J W, LEE J M, KIM S J, et al. Hepatocellular carcinoma: imaging patterns on gadoxetic acid-enhanced MR images and their value as an imaging biomarker[J]. Radiology, 2013, 267(3): 776-786.
33	JOO I, LEE J M. Recent advances in the imaging diagnosis of hepatocellular carcinoma: value of gadoxetic acid-enhanced MRI[J]. Liver Cancer, 2016, 5(1): 67-87.
34	LEE D H, LEE J M, LEE J Y, et al. Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation[J]. J Hepatol, 2015, 62(5): 1122-1130.
35	TOYODA H, KUMADA T, TADA T, et al. Non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of outcomes for early-stage HCC[J]. Hepatol Int, 2015, 9(1): 84-92.
36	GRANATA V, FUSCO R, SETOLA S V, et al. Microvascular invasion and grading in hepatocellular carcinoma: correlation with major and ancillary features according to LIRADS[J]. Abdom Radiol (NY), 2019, 44(8): 2788-2800.
37	AHN S J, KIM J H, PARK S J, et al. Hepatocellular carcinoma: preoperative gadoxetic acid-enhanced MR imaging can predict early recurrence after curative resection using image features and texture analysis[J]. Abdom Radiol (NY), 2019, 44(2): 539-548.
38	LEE S, KIM K W, JEONG W K, et al. Gadoxetic acid-enhanced MRI as a predictor of recurrence of HCC after liver transplantation[J]. Eur Radiol, 2020, 30(2): 987-995.
39	AN C, KIM M J. Imaging features related with prognosis of hepatocellular carcinoma[J]. Abdom Radiol (NY), 2019, 44(2): 509-516.
40	KIM A Y, SINN D H, JEONG W K, et al. Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma[J]. J Hepatol, 2018, 68(6): 1144-1152.
41	CALDERARO J, PETITPREZ F, BECHT E, et al. Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma[J]. J Hepatol, 2019, 70(1): 58-65.
42	WANG M D, LI C, LIANG L, et al. Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma[J]. Oncologist, 2020, 25(10): e1541-e1551.
43	JUNG S M, KIM J M, CHOI G S, et al. Characteristics of early recurrence after curative liver resection for solitary hepatocellular carcinoma[J]. J Gastrointest Surg, 2019, 23(2): 304-311.
44	CHONG H, GONG Y, PAN X, et al. Peritumoral dilation radiomics of gadoxetate disodium-enhanced MRI excellently predicts early recurrence of hepatocellular carcinoma without macrovascular invasion after hepatectomy[J]. J Hepatocell Carcinoma, 2021, 8: 545-563.

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